To compare the Safety and activity of GDC-4198 Alone and in Combination with Giredestrant against Abemaciclib and Giredestrant in Participants with Breast Cancer

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Genentech Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

18 Dec 2025 → ongoing

Decision date (initial)

2025-11-26

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Genentech Inc.

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Pharmacokinetic

Phase Ib Stage: To evaluate the safety of GDC-4198 alone and in combination with giredestrant Phase II Stage: To compare the efficacy of two dose levels of GDC-4198 in combination with giredestrant to the efficacy of abemaciclib in combination with giredestrant

Secondary objectives 6

1. Phase Ib Stage: To make a preliminary assessment of the activity of GDC-4198 alone or in combination with giredestrant
2. Phase Ib Stage: To evaluate food-effect on the pharmacokinetics of GDC-4198 and its metabolites
3. Phase II Stage: To compare the efficacy of two dose levels of GDC-4198 in combination with giredestrant to the efficacy of abemaciclib in combination with giredestrant
4. Phase II Stage: To compare the safety of two doses of GDC-4198 in combination with giredestrant to the safety of abemaciclib in combination with giredestrant
5. Phase II Stage: To characterize the pharmacokinetics of GDC-4198 and its metabolites in combination with giredestrant
6. Phase II Stage:To identify a recommended dose of GDC-4198 for subsequent studies

Conditions and MedDRA coding

Locally Advanced or Metastatic Estrogen Receptor-Positive, human epidermal growth factor receptor 2-negative (HER2-Negative) Breast Cancer who Have Previously Progressed During or After a cyclin-dependent kinase 4/6 (CDK4/6) Inhibitor

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Histologically and/or cytologically confirmed adenocarcinoma of the breast that is locally advanced (not amenable to surgical or radiation therapy with curative intent) or metastatic
2. Previously documented ER+ tumor according to American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP; Allison et al. 2020) or European Society of Medical Oncology (ESMO) guidelines or any national guidelines with criteria conforming to ASCO/CAP or ESMO guidelines
3. Previously documented HER2– tumor according to ASCO/CAP (Wolff et al. 2023) or ESMO guidelines or any national guidelines with criteria conforming to ASCO/CAP or ESMO guidelines
4. Disease progression during or after treatment with an approved CDK4/6 inhibitor (e.g., abemaciclib, palbociclib, ribociclib, etc.) and endocrine therapy (ET) in the locally advanced or metastatic setting
5. Measurable or non-measurable evaluable disease per Response Evaluation Criteria in Solid Tumors (RECIST v1.1)
6. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1

Exclusion criteria 6

1. Advanced, symptomatic, visceral spread that is at risk of life-threatening complications in the short term (including massive uncontrolled effusions [pleural, pericardial, peritoneal] or pulmonary lymphangitis) appropriate for treatment with cytotoxic chemotherapy at time of entry into the study, as per national or local treatment guidelines
2. Have received more than one-line of therapy for locally advanced or metastatic disease
3. Have received prior chemotherapy for metastatic breast cancer
4. Treatment with anti-cancer therapies, including investigational therapies, within 28 days or 5 drug elimination half‑lives, whichever is shorter, prior to initiation of study drug
5. Poor peripheral venous access
6. Malabsorption condition (e.g., active inflammatory gastrointestinal (GI) disease, etc.) or other GI conditions/surgeries that the investigator assesses may significantly interfere with enteral absorption

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 5

1. Incidence and severity of adverse events, with severity determined according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE v5.0) grading scale
2. Change from baseline in selected vital signs
3. Change from baseline in selected clinical laboratory test results
4. Incidence and nature of dose-limiting toxicities (DLTs)
5. Progression-free survival

Secondary endpoints 14

1. Phase Ib Stage: Overall Response Rate (ORR)
2. Phase Ib Stage:Clinical Benefit Rate (CBR)
3. Phase Ib Stage:Area under the concentration time-curve from Time 0 to last measurable concentration (AUC0-t), area under the concentration time-curve from Time 0 to infinity (AUCinf), and maximum serum Concentration (Cmax) following administration of a single dose of GDC-4198 under fasted and fed conditions
4. Phase II Stage: Overall Response Rate (ORR)
5. Phase II Stage:Duration of Response (DOR)
6. Phase II Stage: Clinical Benefit Rate (CBR)
7. Phase II Stage: Overall Survival (OS)
8. Phase II Stage: OS rate at 6 months and 12 months
9. Phase II Stage: PFS rate at 6 months and 12 months
10. Phase II Stage:Incidence and severity of adverse events, with severity determined according to the CTCAE v5.0 grading scale
11. Phase II Stage: Change from baseline in selected vital signs
12. Phase II Stage: Change from baseline in selected clinical laboratory test results
13. Phase II Stage:Plasma concentrations of GDC-4198 and its metabolites at specified timepoints
14. Phase II Stage: Relationship between GDC-4198 dose and safety, pharmacokinetics, and efficacy

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Comparator 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Genentech Inc.

Sponsor organisation

Genentech Inc.

Address

1 Dna Way

City

South San Francisco

Postcode

94080-4918

Country

United States

Scientific contact point

Organisation

Genentech Inc.

Contact name

US Program Manager Product Development Regulatory

Public contact point

Organisation

Genentech Inc.

Contact name

US Program Manager Product Development Regulatory

Third parties 8

Locations

4 EU/EEA countries · 22 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Urgent safety measures 1 · Art. 54 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 35 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications